Genes provide the fundamental instructions for building and operating every cell in the human body. Encoded in DNA, these instructions direct the production of proteins that perform countless tasks, from forming tissues to regulating metabolism. One such gene, RAD51C, plays a specific role in maintaining the integrity of our cellular machinery.
How RAD51C Works in Your Cells
The RAD51C gene is a member of the RAD51 family. The protein produced by RAD51C is involved in homologous recombination, a precise method of DNA repair. This process fixes damaged DNA, particularly double-strand breaks. The RAD51C protein works alongside other RAD51 paralogs to support the assembly and stabilization of DNA repair structures.
During homologous recombination, RAD51C helps facilitate the search for and pairing with a homologous DNA sequence, which acts as a template for accurate repair. This mechanism allows for the exchange of genetic information and the correction of errors, preventing mutations and maintaining genome stability. Without proper DNA repair, cells accumulate errors, leading to genomic instability. RAD51C also contributes to the activation of a checkpoint kinase called CHK2, which helps coordinate cell cycle progression with DNA repair, ensuring damaged cells do not divide prematurely.
RAD51C and Cancer Risk
When the RAD51C gene does not function as it should due to mutations, its ability to repair DNA is impaired. These changes disrupt the precise homologous recombination process, causing DNA damage to accumulate within cells. Unrepaired DNA damage can lead to further genetic alterations, increasing the likelihood that cells will grow uncontrollably and form tumors.
Mutations in the RAD51C gene are linked to an increased risk of certain cancers, particularly ovarian and breast cancer. Women with a RAD51C mutation have an estimated 10-15% lifetime risk for ovarian, fallopian tube, or primary peritoneal cancer, significantly higher than the general population’s 1.3% risk. For breast cancer, women with a RAD51C mutation face about a 20% lifetime risk, compared to approximately 12.5% in the general population. Some studies also suggest a possible association with pancreatic cancer.
In rare instances, inheriting two non-working copies of the RAD51C gene—one from each parent—can lead to Fanconi anemia. This severe genetic disorder is characterized by developmental abnormalities, bone marrow failure, and an increased susceptibility to various cancers, including leukemia and lymphoma.
Passing Down RAD51C Mutations
Mutations in the RAD51C gene are inherited in an autosomal dominant pattern. This means an individual only needs to inherit one copy of the mutated gene from either parent to have an increased cancer risk. Each child of a parent with a RAD51C mutation has a 50% chance of inheriting the same mutation, regardless of gender.
Genetic testing for RAD51C mutations is available and can be considered by individuals with a strong family history of associated cancers, such as ovarian or breast cancer. A genetic counselor can assess an individual’s personal and family health history to determine if testing is appropriate. Identifying a RAD51C mutation allows for informed decisions regarding personalized cancer risk management and can also provide information for other family members who may be at risk.
Living with a RAD51C Mutation
Individuals identified with a RAD51C mutation have several options for managing their increased cancer risk. Increased surveillance is a common approach, involving specific screenings for associated cancers. For example, women with a RAD51C mutation may be advised to undergo yearly mammograms and consider annual breast MRIs starting around age 40, or earlier depending on family history.
Risk-reduction strategies can also be discussed with a healthcare provider. These may include prophylactic surgeries, such as the removal of ovaries and fallopian tubes, to significantly lower ovarian cancer risk. Lifestyle adjustments, while not eliminating risk, can also contribute to overall health. Additionally, certain targeted therapies, like PARP inhibitors, have shown effectiveness in treating cancers with DNA repair deficiencies, including those linked to RAD51C mutations. It is always recommended that individuals with a RAD51C mutation consult with a genetics expert to develop a personalized medical plan.